The neural system underlying taste is, like so many other neural systems, highly complex: the two parallel pathways that carry taste information to the cortex, one of which ascends via thalamus and one via amygdala, cross and feedback at several levels. It is reasonable to hypothesize, therefore, that taste perception and learning may rely on such neural interactions-interactions that, if real, should cause time- varying taste responses that are coupled between regions and covariant with taste acceptance and rejection. In fact, our recent work has revealed just these sorts of taste response dynamics linking basolateral amygdala (BLA) and gustatory cortex (GC), reciprocally connected parts of the forebrain taste circuit. The experiments proposed here will provide the first direct tests of whether such dynamics are a vital part of normal perception. We will use site-specific pharmacology, manipulations of learning, and electrical brain stimulation to perturb BLA-GC functional connectivity, and test whether each manipulation affects the putative temporal codes appropriately, and in lock-step with perception. We will first test whether the presence of hedonic information in the time-course of GC taste responses depends upon amygdala-cortical connectivity by knocking out BLA (using infusions of the GABA agonist muscimol) in awake rats as they (the rats) respond to naturally palatable and aversive tastes. We will then use similar infusions to test whether BLA is important for temporally-specific changes to these GC taste response properties wrought by conditioned taste aversion (CTA), a paradigm whereby rats learn that a taste once thought palatable is in fact noxious. Next, we will examine whether plasticity at amygdala- cortical synapses are the source of learning-related changes in taste dynamics, by infusing a compound that inhibits synaptic plasticity (H-7) just after training sessions. Finally, we will test whether the results of the first 3 experiments occur in variants of the CTA paradigm that do not require BLA, in order to test not only the existence of amygdala-cortical cooperation but its relevance to the specifics of what is learned. Together, these experiments will directly test a uniquely systems-level view of perception and learning, in the process revealing the neural mechanisms of an experiential phenomenon that affects (sometimes adversely) all mammals including humans. PUBLIC HEALTH RELEVANCE: This project investigates the nature of naive and learned emotional responses to tastes-disgust responses generated by a neural system similar to the one underlying fear responses. While most research focuses on describing the role on each individual part (in this case, cortex and amygdala) of such systems, the experiments proposed here will bring a battery of cutting-edge technology to bear on explaining how the interconnected networks of neurons work together to make perception and learning happen. As such, it provides an unprecedentedly sophisticated view of how mammals learn that a stimulus should be thought of as aversive;the knowledge generated by this work bears on a variety of human aversions to food, including those induced by cancer medications, as well as on more general processes relating to normal and abnormal disgust responses.